Prostaglandin production in the umbilical and uterine circulations in pregnant sheep at 129-136 days gestation.

Prostaglandins circulating in the maternal and foetal blood have been implicated in important physiological systems. These functions include foetal adrenal function, maintenance of patency of the ductus arteriosus, regulation of uterine and umbilical circulations, and labor and delivery type myometrial contractions. The placenta is a major site of prostaglandin production in pregnancy. Limited data are available which combine measurements of veno-arterial differences across the uterine and umbilical circulations with blood flow in these circulations to enable calculation of umbilical-placental and utero-placental production rates for the prostaglandins. In chronically instrumented pregnant ewes, between 129 and 136 days of gestation, prostaglandin F2 alpha(PGF2 alpha), 13, 14 dihydro-15-keto prostaglandin F2 alpha (PGFM), prostaglandin E2 (PGE2) were measured in the maternal carotid artery and uterine vein. Foetal PGE2, and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) (the major metabolite of prostacyclin) were measured in umbilical venous and foetal descending aorta arterial plasma. Umbilical and uterine blood flow were measured using the diffusion-equilibrium technique. Uterine blood flow was 1693 +/- 137 ml.min-1 (mean +/- SEM); uterine production rates were 480 +/- 88 ng.min-1 for PGF2 alpha, 517 +/- 144 ng.min-1 for PGFM, and 165 +/- 27 ng.min-1 for PGE2. Umbilical blood flow was 147 +/- 17 ml.min-1.kg-1 foetal body weight. Umbilical production rates into the foetal circulation were 11 +/- 2 ng.min-1.kg-1 for PGE2 and 6 +/- 2 ng. ng.min-1.kg-1 foetal body weight for PGI2.     

Uterine vein prostaglandin levels in late pregnant dogs.

We studied the uterine venous plasma concentrations of prostaglandins E2, F2 alpha, 15 keto 13,14 dihydro E2 and 15 keto 13,14 dihydro F2 alpha in late pregnant dogs in order to evaluate the rates of production and metabolism of prostaglandin E2 and F2 alpha in pregnancy in vivo. We used a very specific and sensitive gas chromatography-mass spectrometry assay to measure these prostaglandins. The uterine venous concentrations of prostaglandin E2 and 15 keto 13,14 dihydro E2 were 1.35 +/- .27 ng/ml and 1.89 +/- .37 ng/ml, respectively; however, we could not find any prostaglandin F2 alpha and very little of its plasma metabolite in uterine venous plasma. Since uterine microsomes can generate prostaglandin F2 alpha and E2 from endoperoxides, prostaglandin F2 alpha production in vivo must be regulated through an enzymatic step after endoperoxide formation. Prostaglandin E2 is produced by pregnant canine uterus in quantities high enough to have a biological effect in late pregnancy; however, prostaglandin F2 alpha does not appear to play a role at this stage of pregnancy.     

The effect of closing the ductus arteriosus on the pulmonary circulation of the fetal sheep

In the mammalian fetus the ductus arteriosus allows right ventricular output to be shunted away from the lungs to the systemic circulation. This study was performed to determine how closing the ductus arteriosus of the fetal sheep would affect the pulmonary circulation. Under halothane anaesthesia 6 near-term fetal sheep were delivered with the umbilical circulation intact. Catheters were placed in the right atrium, the pulmonary artery, and the aorta. Pulmonary blood flow was measured by injecting radioactive microspheres into the right atrium while a reference sample was withdrawn from the pulmonary artery. Closing the ductus arteriosus increased pulmonary arterial pressure by 22% from 51 +/- 3 to 62 +/- 3 mmHg and increased pulmonary blood flow disproportionately by 198% from 232 +/- 74 to 692 +/- 80 ml/min per 100g. Thus, pulmonary vascular resistance decreased by 75% from 0.451 +/- 0.65 to 0.095 +/- 0.010 mmHg 100g min/ml. These findings extend the observation that pressure and flow in the pulmonary circulation of the air-breathing lung do not have a linear relationship passing through the origin to include a striking example in the fluid-filled lung of the intact fetus. They also raise questions about the nature of the elevated vascular resistance in the fetal lung.     

Phosphatidylethanolamine turnover is an early event in the response of NB2 lymphoma cells to prolactin

The effect of prolactin on phospholipid metabolism in the prolactin-dependent rat lymphoma cell line Nb2 was investigated in cells prelabeled with [3H]arachidonic acid or [3H]ethanolamine. Prolactin (20 ng/ml) caused (a) a 20-60% loss of radiolabeled phosphatidylethanolamine within 0.5 to 2 min, (b) a loss of [3H]ethanolamine-labeled phosphatidylethanolamine from crude membranes, (c) a rapid accumulation of [3H]phosphoethanolamine and [3H]ethanolamine, and (d) a transient increase (15 s to 2 min) in prostaglandin F2 alpha and E2. Arachidonic acid (1-2 micrograms/ml) induced Nb2 cell growth but prostaglandin F2 alpha, E2, ethanolamine, and phosphoethanolamine did not. Prostaglandin E2 inhibited while prostaglandin F2 alpha enhanced growth in the presence of prolactin or arachidonic acid. These results suggest that stimulation of Nb2 cell growth by prolactin is linked to activation of a phosphatidylethanolamine-specific phospholipase C. Arachidonic acid and prostaglandin F2 alpha may participate in regulating the mitogenic action of prolactin.     

Prostaglandin E2 in the lung lavage fluid of premature newborns before and after surgical or medical closure of a patent ductus arteriosus

To analyze the role of prostaglandin E2 in maintaining ductal patency in premature newborns, we measured the PGE2 concentration in the lung lavage fluid of nine patients within 24 h before and 4-8 h after surgical ligation of a patent ductus arteriosus and in two patients before and after closure of the ductus following intravenous indomethacin. The concentration of PGE2 ranged from 240 to 3770 pg/ml (mean 1666 +/- 1256 pg/ml) before operative intervention and show a significant decrease to 0-300 pg/ml (mean 93 +/- 106 pg/ml, P less than 0.001, Student's two-tailed t-test) within a few hours after ligation of the ductus arteriosus. The same significant decrease could be seen in two patients with successful indomethacin therapy (0.25 mg/kg in three doses/day) with concomitant ductus closure. In contrast, when indomethacin was given in a reduced dose (0.1 mg/kg in three doses/day), only a slight effect on PGE2 synthesis could be seen without closure of ductus arteriosus. We suggest that the fall of PGE2 levels in lung lavage fluid reflects the local synthesis in the ductus arteriosus itself and is responsible for the decrease induced by surgical ligation or pharmacological inhibition by indomethacin.     

The control of cardiovascular shunts in the fetal and perinatal period

The fetal circulation has two major vascular shunts, the ductus arteriosus and the ductus venosus. The ductus arteriosus connects the pulmonary artery with the descending portion of the aortic arch, hence shunting most of the right ventricular output away from the unexpanded lungs. The ductus venosus connects instead the portal sinus with the inferior vena cava and allows well-oxygenated umbilical vein blood to bypass the liver and reach the central circulation rapidly. Both blood vessels cease their function after birth and undergo permanent closure. It is now well established that prenatal patency of the ductus arteriosus is an active state sustained by a prostaglandin. A similar mechanism has been recently recognized in the fetal ductus venosus. Evidence is presented indicating that prostaglandin E2 and prostaglandin I2 are natural relaxants, respectively, for the ductus arteriosus and the ductus venosus. In addition, both vascular shunts share the dependence on an endogenous cytochrome P-450 mechanism to develop their contractile tone. This mechanism may be important in the normal process of shunt closure at birth. While broadening the knowledge of fetal cardiovascular homeostasis, advances in this field have important implications for the prevention and management of certain pathological conditions affecting the newborn.     

Prostaglandin F2 alpha-induced release of oxytocin from bovine corpora lutea in vitro

Two experiments were conducted to study the in vitro effects of prostaglandins F2 alpha (PGF2 alpha), E2 (PGE2), and luteinizing hormone (LH) on oxytocin (OT) release from bovine luteal tissue. Luteal concentration of OT at different stages of the estrous cycle was also determined. In Experiment 1, sixteen beef heifers were assigned randomly in equal numbers (N = 4) to be killed on Days 4, 8, 12, and 16 of the estrous cycle (Day 0 = day of estrus). Corpora lutea were collected, an aliquot of each was removed for determination of initial OT concentration, and the remainder was sliced and incubated with vehicle (control) or with PGF2 alpha (10 ng/ml), PGE2 (10 ng/ml), or LH (5 ng/ml). Luteal tissue from heifers on Day 4 was sufficient only for determination of initial OT levels. Luteal OT concentrations (ng/g) increased from 414 +/- 84 on Day 4 to 2019 +/- 330 on Day 8 and then declined to 589 +/- 101 on Day 12 and 81 +/- 5 on Day 16. Prostaglandin F2 alpha induced a significant in vitro release of luteal OT (ng.g-1.2h-1) on Day 8 (2257 +/- 167 vs. control 1702 +/- 126) but not on Days 12 or 16 of the cycle. Prostaglandin E2 and LH did not affect OT release at any stage of the cycle studied. In Experiment 2, six heifers were used to investigate the in vitro dose-response relationship of 10, 20, and 40 ng PGF2 alpha/ml of medium on OT release from Day 8 luteal tissue.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of prostaglandin F(2alpha)- thamsalt and Estrumate (ICI 80996) on plasma progesterone levels in Indian water buffaloes (Bubalus bubalis )

Thirty six buffalo showing normal reproductive cyclas were given a single intramuscular injection of prostaglandin F(2alpha)- thamsalt (PGF(2alpha)) and Estrumate on day 9 or 15 of the estrous cycle in order to induce estrus. In PGF(2alpha) treated animals, plasma progesterone dropped from 2.99+/-0.29 to 0.10 +/- 0.02 ng/ml and from 5.53 +/- 0.53 to 0.09 +/- 0.03 ng/ml (mean +/- SEM) within 72 hours of treatment, on day 9 and 15, respectively. Similarly, the treatment with Estrumate on day 9 or 15 of the cycle reduced the level of proges--terone from 3.02 +/- 0.03 to 0.14 +/- 0.03 ng/ml and from 4.26 +/- 0.47 to 0.21 +/- 0.03 ng/ml, respectively, 72 hours aPter each treatment. It was inferred that both drugs induce estrus in buffalo without any observed residual effect.     

Prostaglandin biosynthesis and catabolism in the lamb ductus arteriosus, aorta and pulmonary artery.

Homogenates of tissues from fetal and neonatal lamb ductus arteriosus, aorta and pulmonary artery have the capacity to convert arachidonic acid as well as the intermediate prostaglandin endoperoxide, prostaglandin H2, into three products: prostaglandins E2, F2alpha and a major product 6-ketoprostaglandin F1alpha. The three tissues also displayed prostaglandin 15-hydroxydehydrogenase and 13-reductase catabolic activities. The catabolishing system showed considerable substrate specificity: prostaglandin E1 was a good substrate whereas prostaglandins F1alpha and F2alpha were completely devoid of catabolism. The complete system was observed in immature as well as mature arterial vessels, in the fetus as well as the neonate (up to 7 days old). These experiments demonstrate the presence of several components of the prostaglandin system in these tissues and offer biochemical evidence for the implication of prostaglandins E2 and I2 in the maintenance of the ductus and neighboring vessels in a relaxed state in the fetus.     

Cyclooxygenase-2 inhibitors constrict the fetal lamb ductus arteriosus both in vitro and in vivo

Nonselective cyclooxygenase (COX) inhibitors are potent tocolytic agents; however, they also have adverse fetal effects such as constriction of the fetal ductus arteriosus. Recently, selective COX-2 inhibitors have been used in the management of preterm labor in the hope of avoiding fetal complications. However, both COX-1 and -2 are expressed by cells of the ductus arteriosus. We used fetal lambs (0.88 gestation) to assess the ability of selective COX-2 inhibitors celecoxib and NS398 to affect the ductus arteriosus. Both selective COX-2 inhibitors decreased PGE(2) and 6ketoPGF(1alpha) production in vitro; both inhibitors constricted the isolated ductus in vitro. The nonselective COX-1/COX-2 inhibitor indomethacin produced a further reduction in PG release and an additional increase in ductus tension in vitro. We used a prodrug of celecoxib to achieve 1.4 +/- 0.6 microg/ml, mean +/- standard deviation, of the active drug in vivo. This concentration of celecoxib produced both an increase in pressure gradient and resistance across the ductus; celecoxib also decreased fetal plasma concentrations of PGE(2) and 6ketoPGF(1alpha). Indomethacin (0.7 +/- 0.2 microg/ml) produced a significantly greater fall in ductus blood flow than celecoxib and tended to have a greater effect on ductus resistence in vivo. We conclude that caution should be used when recommending COX-2 inhibitors for use in pregnant women, because COX-2 appears to play a significant role in maintaining patency of the fetal ductus arteriosus.     

Distribution of prostaglandin biosynthetic pathways in organs and tissues of the fetal lamb

Five prostaglandins, i.e. prostaglandins E2, F2alpha and D2, 6-keto-prostaglandin F1alpha and thromboxane B2, were measured by mass spectrometry. Homogenates of fetal lamb brain, lung, liver, spleen and kidney and the ductus arteriosus, aorta and pulmonary artery formed different amounts of each product. Although the main prostaglandin in the fetal organs was prostaglandin E2, arterial tissue formed mostly 6-keto-prostaglandin F1alpha. These results demonstrate significant differences between organs and tissues in the relative direction of the 'prostaglandin synthetase' enzyme complex.     

The content of prostaglandin E and prostaglandin F2alpha in the exudate of carrageenin granuloma of rats.

1.Granuloma was made by the subcutaneous injection of 2% carrageenin solution on the dorsum of male rats. Eight, 16, 24 and 72 h after the injection. the exudate from each rat granuloma was withdrawn and extracted for rpstaglandins. 2.Extracted prostaglandins were separated prostaglandin E and prostaglandin F group by silicic acid mini-column chromatography. Then the amount of prostaglandin E and prostaglandin F2alpha were determined by the radioimmunoassay method. 3.The levels of prostaglandin E in the granuloma exudates were 4.6 ng/ml at 8 h after the carrageenin injection, then decreased 3.6 ng/ml and to 1.1 ng/ml at 16 h and 24 h, respectively. Seventy-two h after the injection, prostaglandin E level was increased to 8.1 ng/ml. 4.The levels of prostaglandin F2alpha in the exudate were as follows: At 8 h after the carrageenin injection, the level was 9.4 ng/ml, then decreased to 1.3 ng/ml and to 0.8 ng/ml at 16 h and 24 h, respectively. Seventy-two h after the carrageenin injection, it was again elevated to 4.7 ng/ml. 5.The exudate of granuloma, 24 and 72 h after the carrageenin injection, was incubated with [3H]prostaglandin E1 at 37 degrees C for 30 min. Then the acidic ether extract was subjected to reversed phase partition chromatography. It was found that the exudate of 24 h and 72 h granuloma had little activity of prostaglandin 15alpha-hydroxy dehydrogenase.     

Formation of prostacyclin (PGI2) by the ductus arteriosus of fetal lambs at different stages of gestation.

Prostaglandins appear to play a role in maintaining patency of the ductus arteriosus during gestation. Prostacyclin (PGI2) is the major product of prostaglandin biosynthesis in the lamb ductus arteriosus. This factor is both a vasodilator and a potent inhibitor of human platelet aggregation. We used inhibition of platelet aggregation as a sensitive bioassay to measure PGI2 generation in rings of ductus arteriosus from fetal lambs. Mechanical manipulation accelerated the rate of PGI2 released from the tissue 10 to 50 times. Tranylcypromine, an antagonist of prostacyclin synthetase, suppressed production of PGI2 by rings of ductus arteriosus. Rings from immature animals (98-103 days gestation, term is 150 days) released significantly more PGI2 (190 +/- 28 ng/g wet weight/ 20 min, n = 9) than did those from near term animals (136-146 days; 106 +/- 23 ng/g wet weight/20 min, n = 10). The capacity of the ductus arteriosus to generate more PGI2 earlier in gestation is consistent with the observation that vessels from animals less than 110 days gestation have a significantly larger indomethacin induced contraction than do vessels near term.     

Determination of prostaglandin F2 alpha, E2, D2 and 6-keto-F1 alpha in human cerebrospinal fluid.

Prostaglandin (PG)F2 alpha, E2, D2 and 6-keto-F1 ALha were determined in human cerebrospinal fluid by a mass spectrometric technique. The samples were obtained from 12 patients with suspected intracranial disease. A 64 fold variation in PG levels was observed. The major PG was 6-keto-F1 alpha (0.12--15 ng/ml). PGF2 alpha and PGE2 were present in lower concentrations PGD2 was below the level of detection (0.05 ng/ml) except in one patient with extremely high total levels of PGs.     

Effect of prostaglandin F2alpha on cells of the mammary gland alveoli in mice

In studies on lactating laboratory mice an influence of prostaglandin F2 alpha on the value of transepithelial potential difference and resistance of the alveolar secretory epithelium in the mammary gland, was studied. Prostaglandin F2 alpha did not affect initial level of transepithelial potential difference and resistance in alveoles. In all experiments with the preliminary application of prostaglandin F2 alpha in different concentrations (1 x 10(-5)-1 x 10(-11) M) was registered a reliable increase in an amplitude (before 31 +/- 2%) and duration (before 43 +/- 3%) to return reactions on oxytocin. Prostaglandin F2 alpha caused a reduction of transepithelial resistance in the alveolar secretory epithelium of first phase to return reaction on oxytocin on 28 +/- 22%. The data obtained indicate a possibility of participation of prostaglandin F2 alpha in development of certain stages of shaping a composition of milk.     

Prostaglandin F2 alpha, oxytocin and progesterone secretion by bovine luteal cells at several stages of luteal development: effects of oxytocin, luteinizing hormone, prostaglandin F2 alpha and estradiol-17 beta

Bovine luteal cells from Days 4, 8, 14 and 18 of the estrous cycle were incubated for 2 h (1 x 10(5) cells/ml) in serum-free media with one or a combination of treatments [control (no hormone), prostaglandin F2 alpha (PGF), oxytocin (OT), estradiol-17 beta (E) or luteinizing hormone (LH)]. Luteal cell conditioned media were then assayed by RIA for progesterone (P), PGF, and OT. Basal secretion of PGF on Days 4, 8, 14 and 18 was 173.8 +/- 66.2, 111.1 +/- 37.8, 57.7 +/- 15.4 and 124.3 +/- 29.9 pg/ml, respectively. Basal release of OT and P was greater on Day 4 (P less than 0.01) than on Day 8, 14 and 18 (OT: 17.5 +/- 2.6 versus 5.6 +/- 0.7, 6.0 +/- 1.4 and 3.1 +/- 0.4 pg/ml; P: 138.9 +/- 19.5 versus 23.2 +/- 7.5, 35.4 +/- 6.5 and 43.6 +/- 8.1 ng/ml, respectively). Oxytocin increased (P less than 0.01) PGF release by luteal cells compared with control cultures irrespective of day of estrous cycle. Estradiol-17 beta stimulated (P less than 0.05) PGF secretion on Days 8, 14 and 18, and LH increased (P less than 0.01) PGF production only on Day 14. Prostaglandin F2 alpha, E and LH had no effect on OT release by luteal cells from any day. Luteinizing hormone alone or in combination with PGF, OT or E increased (P less than 0.01) P secretion by cells from Days 8, 14 and 18. However on Day 8, a combination of PGF + OT and PGF + E decreased (P less than 0.05) LH-stimulated P secretion. These data demonstrate that OT stimulates PGF secretion by bovine luteal cells in vitro. In addition, LH and E also stimulate PGF release but effects may vary with stage of estrous cycle.     

Estrogens and prostaglandin F2alpha in the semen and blood plasma of stallions

A study was performed to determine the levels of estrogens and prostaglandin F(2)alpha in the stallion ejaculate. Simultaneous semen and blood plasma samples were collected from 19 stallions, 2 weeks apart, during the breeding season. Although not statistically different, the total mean estrogen content tended to be higher in seminal plasma (4447 pg/ml) than in blood (2497 pg/ml). A tendency was found for higher mean estrone sulphate concentrations than for total free steroid in both seminal (4116.1 vs 330.5 pg/ml) and blood plasma (2447.1 vs 49.5 pm/ml). Mean concentrations of estrone in ejaculate and blood plasma were 257.1 +/- 267.0 (SD) and 9.5 +/- 5.4 pg/ml, respectively. Estradiol-17beta concentrations were 73.4 +/- 87.4 and 40.0 +/- 27.6 pg/ml in ejaculates and blood plasma, respectively. Mean PGF(2)alpha concentrations tended to be much higher than total estrogens (1106.8 +/- 1636.4, SD, vs approximately 260 ng/ejaculate, respectively). To our knowledge this is the first report of PGF(2)alpha and estrogen concentrations in the stallion ejaculate.     

Cardiovascular effects of prostaglandin I2 and prostaglandin F2 alpha in the unanesthetized bullfrog, Rana catesbeiana

The cardiovascular effects of prostaglandin (PG)I2 and PGF2 alpha were compared in the unanesthetized American bullfrog (Rana catesbeiana). Control mean arterial pressure (MAP) and heart rate (HR) were 25.7 +/- 1.1 mm Hg and 35.1 +/- 1.1 beats/min, respectively. Intravenous injections of PGI2 decreased MAP and increased HR in a dose-dependent fashion over the range of concentrations tested (0.03, 0.3, 3, and 10 micrograms/kg-body weight [bw]. Neither atropine (1 mg/kg-bw) nor verapamil (1 mg/kg-bw) treatment altered the MAP or HR responses to PGI2 (3 micrograms/kg-bw). However, propranolol (5 mg/kg-bw) significantly blunted the hypotensive effects without affecting the increase in HR. Prostaglandin F2 alpha (tested at 0.3, 3, 30, and 100 micrograms/kg-bw) increased both MAP and HR. Mean arterial pressure increased with concentrations greater than 0.3 microgram/kg-bw and reached peak effects at 30 micrograms/kg-bw. Prostaglandin F2 alpha increased HR at doses greater than 0.3 microgram/kg-bw. Neither the pressor nor positive chronotropic effects of PGF2 alpha (30 micrograms/kg-bw) were affected by atropine or propranolol. However, verapamil significantly attenuated the pressor effects without affecting the increase in HR. These results demonstrate that both prostaglandins have qualitatively similar effects on HR, but opposite effects on MAP. Prostaglandin I2 is a hypotensive prostaglandin, while PGF2 alpha is hypertensive. The pressor effects of PGF2 alpha are partially dependent on calcium influx. The positive chronotropic effects of both prostaglandins are independent of the autonomic nervous system, suggesting a different mechanism of action.     

Prostaglandin E2 induced changes in renal blood flow, renal interstitial hydrostatic pressure and sodium excretion in the rat

Prostaglandin E2, when infused into the renal artery of the dog, is a vasodilator and increases both renal interstitial hydrostatic pressure and sodium excretion. Similar studies in the rat, however, have been inconclusive. The present study examined the effect of prostaglandin E2 infusion into the renal interstitium, by means of a chronically implanted matrix, on renal blood flow, renal interstitial hydrostatic pressure and sodium excretion in the rat. Prostaglandin E2 was continuously infused directly into the kidney interstitium to mimic endogenous prostaglandin E2 production by renal cells. The maximum change in each of these parameters occurred when 10(-5) M PGE2 was infused. Renal blood flow increased from 4.70 +/- 0.91 to 5.45 +/- 0.35 ml/min (p less than 0.05) while renal interstitial hydrostatic pressure decreased from 3.9 +/- 0.4 to 2.6 +/- 0.5 mmHg (p less than 0.05) and fractional excretion of sodium decreased from 1.02 +/- 0.20 to 0.61 +/- 0.12% (p less than 0.05). Thus, the present study demonstrates that renal interstitial infusion of prostaglandin E2 increases total renal blood flow but decreases both renal interstitial hydrostatic pressure and urinary sodium excretion in the rat.     

Potential role for prostaglandin F2 alpha, D2, E2 and thromboxane A2 in mediating the metabolic and hemodynamic actions of sympathetic nerves in perfused rat liver

In isolated rat liver perfused at constant pressure perivascular nerve stimulation caused an increase of glucose and lactate output and a reduction of perfusion flow. The metabolic and hemodynamic nerve effects could be inhibited by inhibitors of prostanoid synthesis, which led to the suggestion that the effects of nerve stimulation were, at least partially, mediated by prostanoids [Iwai, M. & Jungermann, K. (1987) FEBS Lett. 221, 155-160]. This suggestion is corroborated by the present study. 1. Prostaglandin D2, E2 and F2 alpha as well as the thromboxane A2 analogue U46619 enhanced glucose and lactate release and lowered perfusion flow similar to nerve stimulation. 2. The extents, the kinetics and the concentration dependencies of the metabolic and hemodynamic actions of the various prostanoids were different. Prostaglandin F2 alpha and D2 caused relatively stronger changes of metabolism, while prostaglandin E2 and U46619 had stronger effects on hemodynamics. Prostaglandin F2 alpha elicited greater maximal alterations than D2 with similar half-maximally effective concentrations. Prostaglandin F2 alpha mimicked the nerve actions on both metabolism and hemodynamics best with respect to the relative extents and the kinetics of the alterations. 3. The hemodynamic effects of prostaglandin F2 alpha could be prevented completely by the calcium antagonist nifedipine without impairing the metabolic actions of the prostanoid. Apparently, prostaglandin F2 alpha influenced metabolism directly rather than indirectly via hemodynamic changes. The present results, together with the previously described effects of prostanoid synthesis inhibitors, suggest that prostanoids, probably prostaglandin F2 alpha and/or D2, could be involved in the actions of sympathetic hepatic nerves on liver carbohydrate metabolism. Since prostanoids are synthesized only in non-parenchymal cells, nervous control of metabolism appears to depend on complex intra-organ cell-cell interactions between the nerve, non-parenchymal and parenchymal cells.